Abstract 37: Effect of Fish Oil on Coagulation and Fibrinolysis: A Double-blind Randomized Trial in Obese Adolescents

Abstract

Background: A hypercoagulable state is reported in obese children and adolescents. Fish oil may reduce the propensity for thrombosis by favorably impacting coagulation and fibrinolysis. We hypothesized that pharmacologic fish oil supplementation would reduce the concentration of coagulation factors such as total-fibrinogen (T-Fib) and gamma prime fibrinogen (γ’-Fib) and fibrinolysis factors such as plasminogen activator inhibitor-1 (PAI-1) in obese dyslipidemic adolescents. Methods: Participants (n=42, age 14±2 years) with hypertriglyceridemia and low-density lipoprotein (LDL) cholesterol <160 mg/dL were enrolled in a randomized, doubleblind, crossover trial comparing 4 g of fish oil daily with placebo. Treatment interval was 8 weeks with a 4-week washout. Glucose, insulin, high-sensitivity C-reactive protein (CRP), interleukin-6 (IL-6), T-Fib, γ’-Fib and PAI-1 were measured pre- and post-intervention or placebo. Results: PAI-1 significantly decreased (p = 0.03) with a trend towards a decrease in T-Fib in the fish oil group. Fish oil treatment group also showed significant decrease in γ’-Fib, but not in the placebo group; mean change (95% CI): -0.11 (-0.16, -0.06) vs -0.03 (-0.08, 0.02). The difference in the mean change in γ’-Fib concentration from baseline or washout measures between fish oil treatment and placebo was significant; reg coeff (SE):0.08 (0.03); p=0.02. The change in γ’-Fib was related to the change in log transformed PAI-1 (reg coeff (SE): -0.09 (.041); p=0.03). Further, log-transformed CRP and IL-6 (reg coeff (SE): 0.064 (.030), p=0.04) and 0.10 (.04); p=0.03 respectively) showed significant correlations with baseline or washout baseline γ’ fibrinogen, but there were no such relationships for mean changes. Conclusions: Fish oil-induced synchronized reduction of γ’-Fib, T-Fib and PAI-1 suggests attenuation of the obesity-related alterations in coagulation and fibrinolysis in adolescents. Intriguingly, these changes are independent of changes in other inflammatory factors. The reduction in elevated concentration of γ’-Fib is remarkable as it forms clots that are more fibrinolysis resistant. Further evaluation is warranted on the specific beneficial effect of fish oil on the obesity-related hypercoagulant-/hypofibrinolytic-state and the potential for thrombosis later in life.